Beyond Seizures: Novel applications of a common anti-epileptic drug

Author: Austin Kerns, DVM, MS, DACVIM (Neurology)

Keppra as a Neuroprotective agent

Keppra (levetiracetam) is an anti-epileptic drug that is familiar to most veterinarians. It is commonly used in human and veterinary medicine for the treatment/control of focal and generalized seizures. But in addition to its neuromodulatory and neuroinhibitory effects, multiple studies have suggested neuroprotective properties for keppra in both epileptic and non-epileptic conditions.  Research indicates that it may help protect neurons from damage caused by excitotoxicity, oxidative stress, and inflammation, which are common contributors to neurodegenerative diseases and brain injuries. Its ability to modulate synaptic transmission and reduce the release of pro-inflammatory cytokines enhances its protective profile. The capability of keppra to augment glial glutamate transporters has been proposed as one of the foremost mechanisms through which keppra mediates its neuroprotective properties. This hypothesis fits well with one common change detected following most brain insults – increased concentration of glutamate in the extracellular areas causing enhanced activation of NMDA and AMPA receptors on neurons which results in neurodegeneration. Studies have shown that Keppra may improve outcomes in conditions such as traumatic brain injury and stroke (both ischemic and hemorrhagic), supporting its use as a therapeutic agent in preserving neuronal health and function in various neurological disorders.

Keppra in Sleep Behavior Disorder

Another somewhat novel use of Keppra is in treatment of patients with Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD).  REM sleep disorder is characterized by dream enactment behavior and abnormal muscle tone during REM sleep (muscle tone and movement is normally inhibited during REM sleep). Dream enactment is highly variable and ranges from vocalizations to violent thrashing in bed.  For reasons that are not understood, we sometimes see this arise in veterinary patients who have suffered a cranial cervical spinal cord injury, such a cervical ischemic stroke. In humans with RBD, medications from various classes have been found to be efficacious, including benzodiazepines, melatonin, cholinesterase inhibitors, dopamine agonists, and others, and more recently, Keppra has been reported as a helpful drug in the control of these disruptive and sometimes dangerous movements.  I have had several patients over the years who appear to “act out their dreams” following high cervical spinal cord injuries, and have trialed, with apparent success, oral keppra in these patients.

Just for fun: Does IV keppra need to be diluted and given slowly?

Many veterinarians and technicians are taught that when keppra, a drug utilized commonly in emergency situations, is given intravenously, it must be diluted and given over 5-15 minutes. Indeed, Plumbs states that “In humans, it is recommended that IV doses be diluted in 100 mL of a compatible diluent or diluted to a maximum concentration of 15 mg/mL and administered over 5 to 15 minutes”.  However, a 2021 paper published in the journal Epilepsia, titled “Rapid Administration of Undiluted Intravenous Levetiracetam” investigated whether dilution and slow administration are necessary. They found that in 953 patients administered undiluted doses of keppra (over 8500 hundred rapid IV doses were administered to these patients overall), there were 12 patients with documented adverse drug events, with four potentially directly related to IV keppra administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line.  At our hospital, we routinly administer undiluted keppra intravenously as a bolus and have not documented any adverse effects.